Frequently Asked Questions: How GDUFA Affects Abbreviated New Drug Application (ANDA) Submissions

Receiving a Generic Drug Submission

Q1. What does a refuse-to-receive decision mean?

A refuse-to-receive (RTR) decision indicates that FDA has determined an ANDA is incomplete, usually because of omissions. The ANDA Submissions: Refuse-to-Receive Standards guidance for industry describes what should be included in an ANDA and a prior approval supplement (PAS) to an ANDA and highlights serious deficiencies that may cause FDA to refuse to receive an ANDA.

Q2. What happens if FDA identifies deficiencies in an ANDA?

FDA intends to work with an applicant if FDA determines that an ANDA contains fewer than ten minor deficiencies. In such a case, FDA will notify the applicant by phone, email, or fax. If the applicant satisfactorily amends the ANDA to correct the identified deficiencies within five (5) business days and FDA makes the determination to receive the application as amended, the application will be considered received as of the date on which it was first submitted. If within five business days the requested information has not been submitted, FDA will refuse to receive the ANDA.
If FDA determines that an ANDA contains ten or more minor deficiencies, or one or more major deficiencies, FDA will find that the ANDA does not contain the information required in section 505(j) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and 21 CFR 314.94 and is incomplete. In such cases, FDA will send a letter refusing to receive the ANDA.
The sponsor may decide to submit additional materials to correct the deficiencies, but the resulting amended ANDA will be considered a new ANDA submission, received as of the new date, requiring a new GDUFA fee.

Q3. What happens if a Drug Master File is not available for reference?

Any generic drug submission submitted on or after October 1, 2012, that references, by a letter of authorization, a Type II active pharmaceutical ingredient (API) drug master file (DMF) that has not been deemed available for reference shall not be received. It is highly recommended to have the DMF available for reference at least six months prior to submitting a new ANDA. FDA will conduct a completeness assessment of Type II API DMFs. If a Type II API DMF is paid and is not been deemed available for reference (on FDA’s Available for Reference list) at the time of submission, the ANDA may be refused for receipt.

Q4. What actions must be taken if an inactive ingredient is not in the inactive ingredient database?

For any inactive ingredient that cannot be justified via the inactive ingredient database (IID), the applicant (or ANDA holder) should submit or provide any of the following:
- Pharmacology/toxicology information
- Evidence of a CDER-approved drug product of the same route of administration as the test product that contains the inactive ingredient in question at or above the proposed level of use
- A Controlled Correspondence requesting an evaluation of the acceptability of the proposed level of use.
If the proposed level of use cannot be justified via the IID and none of the above support is provided at the time of submission, the ANDA will be refused for receipt

Application Goal Dates

Q5. How are ANDA goal dates determined?

Applications received in paper format after October 1, 2012, will not be included as part of the new performance metrics established in GDUFA.
ANDAs will be categorized according to cohort year. Once an ANDA is in a given year’s cohort, dates of submission of a subsequent amendment will not change the cohort year. Any additional time periods to be added to the base review period will be calculated using the time periods corresponding to the original cohort year.
Goal dates for generic drug submissions are based on category and cohort year. A summary of these action goals are illustrated in the table below.

*10 months if inspection required

** One additional month added to goal if clinical review division input required

The majority of review goals for original ANDAs and their amendments, and goals for controls do not take effect until year three of GDUFA, which goes from October 1, 2014 to 9/30/2015.
All amendment metric goals are incremental, and the time periods specified are calculated from the date of submission. They will be added to the original review goal, but in no case shall they shorten the original goal date. (In other words, an amendment with a six-month metric which was submitted four months prior to original goal date would add two months to the review clock).
The tier type determines how review goals will apply to amendments. The different tiers and the effect on the goals of the different tiers are explained in the GDUFA Commitment Letter.

Q6. What actions can FDA take on an application?

Post Complete Response Teleconference Meeting Request

Q7. How do I request a teleconference with FDA to discuss deficiencies noted in a Complete Response letter?

Within 10 business days after FDA issues a first-cycle review complete response letter, a 30-minute teleconference may be requested to discuss the deficiencies noted in the letter.
The request must be submitted in writing to the ANDA file and appropriately identified on its cover page as a “Post Complete Response Teleconference Meeting Request.” The request must include a list of specific written questions for discussion, and the scope of the questions should be limited to the content of FDA’s complete response letter.
The meeting request can be granted and held via teleconference, responses to the sponsor’s questions can be responded to in writing in lieu of a teleconference, or the meeting request can be denied.

Additional Resources